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Grand Challenges is a family of initiatives fostering innovation to solve key global health and development problems. Each initiative is an experiment in the use of challenges to focus innovation on making an impact. Individual challenges address some of the same problems, but from differing perspectives.

Ranjan Kanti Panda of the Child in Need Institute in India in collaboration with the International Center for Research on Women, and Accenture for the "Couple Power" project, will evaluate their approach to motivate women between 15-24 years old to have their say in sexual and reproductive health decisions at home, thereby improving maternal and family health in India. The project will use digital technology and is designed to engage both men and women in couples and families to encourage equality within relationships. They will hold two four-day workshops for a group of 140 young couples across two districts to train them to act as role models and teachers for other couples in their communities to help change gender norms and roles. A digital application will be built to collect and analyze the data, and to track vulnerable couples.

Cirle WarrenUniversity of VirginiaCharlottesville, Virginia, United States

Grand Challenges Explorations

Enteric Disease Models

15 Apr 2014

Cirle Warren of the University of Virginia in the U.S. will develop a three dimensional cell culture model (organoid) of the human intestine to study diarrheal diseases. They will build the organoids in a bioreactor using three intestinal cell types, and test different scaffolds to simulate the complex cellular and structural architecture of the human gut. The organoids will then be infected with Cryptosporidium, a common cause of diarrhea in developing countries, and analyzed for altered structural and molecular characteristics to gain insight into the host infection response. This model could also be used to identify new drug targets and evaluate candidate drugs.

Bill Thies and the team of 99DOTS aim to achieve 99% TB drug adherence using a combination of basic mobile phones and augmented blister packaging to provide real-time medication monitoring at drastically reduced cost. The approach is to utilize a custom envelope, or blister card, into which each pack of medication is inserted and sealed by the care provider. When the patient dispenses medication from the blister pack, the pills also break through perforated flaps on the blister card. On the back side of each flap is a hidden number. Patients submit these numbers using their mobile phone as evidence that they have dispensed medication. To avoid incurring any mobile charges, the numbers are used to complete a phone number and deliver a "Missed call" (Missed calls are free if they are not pointed to a VoiceMail). Using this system patients also receive a series of daily reminders (via SMS and automated calls). Missed doses trigger SMS notifications to care providers, who follow up with personal, phone-based counseling. Real-time adherence reports are also made available on the web.

Anastasios Tsaousis of the University of Kent in the United Kingdom will build a screening platform to identify drugs that can be used to treat diarrhea caused by the parasite Cryptosporidium, which is the second major cause of death in children under five years old in developing countries. There are currently no effective drugs for treating Cryptosporidium, largely because it cannot easily be grown in the laboratory making it difficult to study and test for new drugs. They have developed a two-dimensional cell culture system using a specific cell type that can be stably infected with Cryptosporidium and cultivated long term. They will use the CRISPR/Cas9 gene modification technique to alter selected Cryptosporidium genes for monitoring parasite growth, and use it in their cell culture system to screen a library of FDA-approved drugs to identify candidate drugs that block Cryptosporidium growth.

Warren Zipfel of Cornell University in the U.S. will develop a simple, low-cost method to quantify levels of the tuberculosis-causing bacteria Mycobacterium tuberculosis in different tissues by measuring fluorescence emitted by one of its proteins, F420. To decrease the cost they will use a pulsed laser diode for F420 excitation, and analog electronics to process the fluorescence signal. They will optimize the detection circuitry and optics components, and evaluate its sensitivity and capacity for quantifying the bacteria in sputum and lung tissue. They will also build prototypes of the circuitry coupled to various optical instruments such as a laser-scanning microscope for analyzing extracted samples, and a bronchoscope for inserting into the lungs.

Honorine Ward of Tufts Medical Center in the U.S. will develop a three-dimensional model of the human intestine for rapid screening of drugs targeting the parasite Cryptosporidium, which causes potentially lethal diarrhea in young children in developing countries. Developing drugs against Cryptosporidium has been particularly difficult, partly because of the limited understanding of the parasites behavior in the human intestine, and particularly of the effect of malnutrition, which commonly co-occurs with infection and likely contributes to disease severity. They will build a three-dimensional model of the human intestine using a scaffold of silk proteins and a hollow lumen structure lined with cells derived from human intestinal stem cells supported by underlying human myelofibroblasts. They will infect their cell model with fluorescently labelled Cryptosporidium to evaluate how the parasite affects the intestine, and to determine its capacity for high-throughput drug screens.

Kelly JohnstonLiverpool School of Tropical MedicineLiverpool, United Kingdom

Grand Challenges Explorations

Neglected Tropical Diseases

8 Oct 2013

Kelly Johnston and others from the Liverpool School of Tropical Medicine in the United Kingdom will develop a cell line from a parasitic filarial nematode worm that can proliferate continuously in vitro to enable high-throughput screening of candidate anti-filarial drugs. Current drug screening efforts are limited by the complex life cycle of the worms and the difficulties of obtaining sufficient numbers of worms. They will isolate worm cells from various life cycle stages and use a high-content screening approach to monitor thousands of cells cultured under different conditions to increase the probability of detecting a stably growing cell line. Once one or more stable cell lines have been produced, they will establish optimal culture conditions for drug screening assays.

Oscar Noya at the Instituto de Medicina Tropical in Venezuela will develop a simple, low-cost test based on the detection of parasite antigens that can be used to diagnose malaria in low-resource settings. They have developed a multi-antigen blot assay that can diagnose 26 diseases at the same time using saliva or small volumes of blood at low cost without the need for specialized equipment. They will use bioinformatics tools to select synthetic peptides from the malaria-causing parasite Plasmodium falciparum, and from other common pathogens such as HIV and dengue virus. The synthesized peptides will be spotted on cellulose paper and tested for their ability to detect the corresponding disease from sera and saliva samples taken from at-risk populations.

L. David SibleyWashington University in St. LouisSt. Louis, Missouri, United States

Grand Challenges Explorations

Human and Animal Health

10 Oct 2013

L. David Sibley at Washington University in St. Louis in the U.S. is developing a long-term in vitro intestinal epithelial culture system for the intracellular parasite Cryptosporidium, which causes severe diarrheal disease in both humans and animals, and is refractory to many anti-parasitic drugs. Currently, Cryptosporidium can only be grown in infected calves or in short-term in vitro cultures, which cannot be used for the high-throughput chemical screens needed to identify new drugs. In Phase I, they optimized the in vitro culture of isolated intestinal stem cells from human and mouse biopsies, and identified factors to control their differentiation into primary epithelial monolayers, which can better support the growth of intestinal pathogens. This led to around a five-fold increase in the rate of asexual replication of Cryptosporidium, which was enough to successfully test a chemical growth inhibitor. In Phase II, they will further improve culture conditions to support longer-term in vitro growth of Cryptosporidium, which will then be tested for stability and infectivity. They will also develop antibodies against specific developmental stages to help identify culture conditions that enable the parasite to undergo a complete life cycle, which will be valuable for culturing and screening efforts.

Edwin Routledge of Brunel University in the United Kingdom will work towards developing an artificial snail decoy to attract the parasite Schistosoma mansoni, which causes chronic disease. The parasites first develop inside aquatic snails, which they locate via chemical cues (chemoattractants), before they can infect humans. Routledge will identify the relevant chemoattractants by isolating and fractionating chemicals from the snails, and test the ability of these chemicals to attract the parasites. Effective chemoattractants will be characterized and ultimately incorporated into a biodegradable matrix to generate an artificial snail that is easy to deploy in the field and can trap and destroy the parasites, thereby reducing human transmission.

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